Background Pain from skeletal metastases represents a major burden of advanced disease from solid tumors. Analgesic medications, bisphosphonates, hormonal agents, cytotoxic chemotherapy, and external beam radiotherapy are all effective treatments. However, patients often suffer from diffuse painful metastases and respond poorly to these standard therapies. Bone-seeking radionuclides can specifically target osteoblastic lesions to offer palliation of pain. Methods This article offers a narrative review of bone-seeking radionuclides, examines the evidence of safety and efficacy for the treatment of painful skeletal metastases, and presents guidelines for their appropriate use in this patient population. Results Seven bone-seeking radionuclides have shown evidence of both safety and efficacy in reducing pain from diffuse skeletal metastases. 153Sm-EDTMP and 89Sr are most commonly used in the United States and have been safely utilized for both repeat dosing as well as concurrent dosing with cytotoxic chemotherapy. Conclusions Targeted bone-seeking radionuclides are underutilized in the treatment of painful diffuse osteoblastic metastases. Several new agents are in active clinical investigation, and the pending approval of the first alpha-emitting radionuclide (223Ra) may offer a new class of agents that provide greater efficacy and less toxicity than those currently available for routine clinical use.
